Prevalence of Brucella endocarditis: A systematic review and meta‐analysis

Abstract Background Endocarditis caused by Brucella infection is one of this infection's complications, including a high mortality rate. However, studies on the prevalence of this complication have been limited to some case reports. This study investigated the prevalence of Brucella endocarditis globally using a systematic review and meta‐analysis. Methods PubMed, Scopus, and Web of Science databases were searched using appropriate keywords until September 2022. All studies reporting the prevalence of endocarditis in patients with brucellosis were included in this current study. To investigate the pooled prevalence of Brucella endocarditis, random model was used in comprehensive meta‐analysis software. Results A total of 25 studies met the inclusion criteria and were included in the systematic review and meta‐analysis. The prevalence of Brucella endocarditis was 1.3%, and the death rate was 26.5%. The results did not show a significant difference in the prevalence of this complication in different regions. Conclusion According to this study's results, the prevalence of Brucella endocarditis is low, but it includes a large percentage of the deaths of affected patients. To complete our understanding of this complication and its management, more research should be done to investigate the effect of other factors, such as age and gender.


| Study selection
Two independent authors reviewed titles and abstracts, and irrelevant articles were excluded. Full texts of potentially relevant papers have been obtained and were independently reviewed by two authors. All disagreements were discussed to reach a consensus.

| Data curation
For data extraction, two authors independently reviewed all eligible articles and extracted the following data: first author, publication year, study country, continent, and sample size (infected patients with brucellosis, those with endocarditis). A consensus and discussion resolved any disagreement between the researchers. This study selection process was presented in a Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) flowchart ( Figure 1).

| Risk of bias assessment
The quality of included studies was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist.
This prevalence survey assessment checklist includes nine basic questions. These questions focus on a suitable sampling frame, research objectives, and sufficient data analysis. Each item is rated yes, no, or unclear. A "yes" response was scored 1 point, and "no" and "unclear" responses were scored 0 points.
Finally, the average score for each article was independently assessed by two reviewers, and disagreements were resolved by consensus. 9

| Data synthesis
Data analysis of the prevalence of endocarditis in patients with brucellosis was calculated with comprehensive meta-analysis software. A random-effects model was used to estimate the pooled prevalence of endocarditis in patients with brucellosis with 95% CI. 10 Heterogeneity between studies included in the meta-analysis was assessed using the I 2 statistic. I 2 ≤ 25% indicates low homogeneity and, 25% <I 2 ≤ 75% moderate heterogeneity, and I 2 > 75% indicated high heterogeneity. 11 Sensitivity analysis was performed to examine the effect of removing individual studies to examine on the effect of the study on the overall result. 12 Graphical and statistical methods are used to check for publication bias. A well-known graphical method is the examination of funnel plots. The purpose of this method is to produce a scatterplot with the effect sizes on the horizontal axis and a measure of the size of each study on the vertical axis. 13 The Bagg test is a statistical technique for assessing publication bias that assesses whether there is a significant correlation between the ranks of the effect estimates and the ranks of their variances. Results were assumed to have publication bias with p < 0.05. 14

| Subgroup analysis
Subgroup analyzes were performed for publication year, country, continent, and mortality frequency.

| Study search
A total of 1466 publications were identified, and after reviewing, 988 studies were excluded, and 112 articles were analyzed for full-text validation. After a full-text review, 25 published studies met the inclusion criteria and were used for the meta-analysis. Figure 1 illustrates the article review and selection process according to the PRISMA statement.
And, characteristics of included studies are shown in Table 1.

| Prevalence of BE
Publication bias results were shown in funnel plots ( Figure 2). In addition, Begg's test was used to indicate publication bias (p = 0.96). Sensitivity analysis was performed, and the result showed that none of the studies affected the prevalence of endocarditis, as shown in the forest plot of the sensitivity analysis ( Figure 3).
In this study, 5805 brucellosis cases from nine countries were investigated. The pooled prevalence of BE was estimated at 1.3% (95% CI: 0.9%−1.9%; I 2 = 48.8%; p = 0.003) (Figure 4).     Although brucellosis is generally a problem in third world countries, especially countries in the Middle East, our results showed that the prevalence of endocarditis in the two continents of Asia and

| Subgroup analysis
Europe is almost the same, with prevalence rates of 1.3% and 1.7%, respectively. These results emphasize that BE is a paramount public health concern in high-risk and low-risk areas.
We also checked whether the prevalence of BE has changed over the years. The analysis showed that the prevalence of this complication caused by brucellosis had almost the same pattern over